# US 8,772,304 B2 · Benzimidazole inhibitors of leukotriene production

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- Number: US 8,772,304 B2
- Document ID: US8772304B2
- Status: Granted
- Kind: B2
- Application number: 13/281,687
- Filed: 2011-10-26
- Published: 2012-11-01
- Granted: 2014-07-08
- Earliest claimed: 2010-11-01
- Assignees: Boehringer Ingelheim International GmbH
- Applicants: Stephane De Lombaert; Weimin Liu; Ho Yin Lo; Peter Allen Nemoto
- Inventors: Stephane De Lombaert; Weimin Liu; Ho Yin Lo; Peter Allen Nemoto
- Web page: https://patentgrep.com/patent/US8772304B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds of formula (IA), (IB) and (IC): and pharmaceutically acceptable salts thereof, wherein R1-R7 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

## Claims

### Claim 1

A compound of formula IA
wherein:
R1 is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, imidazopyridinyl, pyrazolopyridinyl or dihydropyrrolopyridinyl optionally substituted with oxo, wherein each heterocycle is optionally independently substituted with one to three groups selected from Ra, Rb and Rc;
R2 is C1-C6 alkyl or C3-6 cycloalkyl optionally substituted with C1-3 alkyl;
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9 or 5-6 membered heteroaryl ring which is optionally substituted with C1-3 alkyl;
R4, R5, and R6 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6cycloalkyl
(i) —S(O)nC1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a5-6 membered heterocyclic ring;
R8 and R9 are each independently selected from —H, C1-6alkyl, and 5-6 membered heterocyclic ring;
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and —OH;
R10and R11 are each independently selected from —H, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with halogen and C1-6alkyl-aryl;
n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A compound of formula (IA) according to claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from:
R2 is methyl, ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein the cycloalkyl group is optionally substituted with a C1-3 alkyl group;
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein the heteroaryl ring is optionally substituted with C1-3 alkyl;
R4, R5 and R6 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6cycloalkyl
(i) —S(O)nC1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
R8 and R9 are each independently selected from —H, C1-6alkyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with fluoro and C1-6alkyl-phenyl;
n is 0,1 or 2.

### Claim 3 (depends on 1)

A compound of formula (IA) according to claim 1, wherein:
R1 is selected from:
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11,—NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-fluorpyridine and C1-6alkyl-phenyl;
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

A compound of formula (IA) according to claim 1, wherein:
R2 is methyl, ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, cyclopropyl, cyclobutyl or cyclopentyl, wherein the cycloalkyl group is optionally substituted with methyl;
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

A compound of formula (IA) according to claim 1, wherein:
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein the heteroaryl ring is optionally substituted with C1-3 alkyl;
R4, R5 and R6 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1 -6alkyl, or —OC3-6cycloalkyl
(i) —S(O)2C1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
R8 and R9 are each independently selected from —H, C1-6alkyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

A compound of formula (IA) according to claim 1, wherein:
R1 is selected from:
R2 is t-butyl or cyclobutyl optionally substituted with a methyl group;
R3 is —H, C1-3 alkoxy, —COOR8, —C(O)NR8R9 or triazolyl which is optionally substituted with a methyl group;
R4, R5 and R6 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1 -6alkyl, or —OC3-6cycloalkyl;
R8 and R9 are each independently selected from —H and C1-6alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 6)

A compound of formula (IA) according to claim 6, or a pharmaceutically acceptable salt thereof, wherein:
R1 is

### Claim 8 (depends on 6)

A compound of formula (IA) according to claim 6, wherein:
R2 is t-butyl or cyclobutyl optionally substituted with a methyl group;
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 6)

A compound of formula (IA) according to claim 6, wherein:
R1 is
R2 is t-butyl;
R3 is selected from
R4, R5 and R6 are each independently selected from —H, —CN, F, cyclopropyl, methoxy and t-butoxy;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 9)

A compound of formula (IA) according to claim 9, wherein:
R2is
or a pharmaceutically acceptable salt thereof.

### Claim 11

A compound of formula IB
wherein:
R1 is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, imidazopyridinyl, pyrazolopyridinyl or dihydropyrrolopyridinyl optionally substituted with oxo, wherein each heterocycle is optionally independently substituted with one to three groups selected from Ra, Rb and Rc;
R2 is C1-C6 alkyl or C3-6 cycloalkyl optionally substituted with C1-3 alkyl;
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9 or 5-6 membered heteroaryl ring which is optionally substituted with C1-3 alkyl;
R5, R6, and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1 -6alkyl, or —OC3-6cycloalkyl
(i) —S(O)nC1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2 heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a 5-6 membered heterocyclic ring;
R8 and R9 are each independently selected from —H, C1-6alkyl, and 5-6 membered heterocyclic ring;
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with halogen and C1-6alkyl-aryl;
n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 11)

A compound of formula (IB) according to claim 11, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from:
R2 is methyl, ethyl, propyl, isopropyl, dimethylpropyl, butyl, t-butyl, isobutyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein the cycloalkyl group is optionally substituted with a C1-3 alkyl group;
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein the heteroaryl ring is optionally substituted with C1-3 alkyl;
R5, R6 and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6cycloalkyl
(i) —S(O)nC1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2 heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
R8 and R9 are each independently selected from —H, C1-6alkyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1—C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-fluoropyridine and C1-6alkyl-phenyll;
n is 0, 1 or 2.

### Claim 13 (depends on 11)

A compound of formula (IB) according to claim 11, wherein:
R1 is selected from:
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl—5-6 membered heterocyclyl, C1-6alkyl-fluoropyridine and C1-6alkyl-phenyl;
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 11)

A compound of formula (IB) according to claim 11, wherein:
R2 is methyl, ethyl, propyl, isopropyl, dimethylpropyl, butyl, t-butyl or isobutyl;
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 11)

A compound of formula (IB) according to claim 11, wherein:
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein the heteroaryl ring is optionally substituted with C1-3 alkyl;
R5, R6 and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6 cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6cycloalkyl
(i) —S(O)2C1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2 heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
R8 and R9 are each independently selected from —H, C1-6alkyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 11)

A compound of formula (IB) according to claim 11, wherein:
R1 is selected from:
R2 is t-butyl or dimethylpropyl;
R3 is —H, C1-3 alkoxy, or triazolyl which is optionally substituted with a methyl group;
R5, R6and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl,
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6 cycloalkyl,
(i) morpholinyl or piperidinyl;
R8 and R9 are each independently selected from —H and C1-6alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 16)

A compound of formula (IB) as described in claim 16, or a pharmaceutically acceptable salt thereof, wherein:
R1 is

### Claim 18 (depends on 16)

A compound of formula (IB) as described in claim 16, wherein:
R2 is t-butyl or dimethylpropyl;
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 16)

A compound of formula (IB) according to claim 16, wherein:
R1is
R2 is t-butyl or dimethylpropyl;
R3 is selected from
R5, R6 and R7are each independently selected from —H, —CN, F, Cl, Br, methyl, morpholinyl and methoxy;
or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 19)

A compound of formula (IB) according to claim 19, wherein:
R2 is t-butyl;
R3 is selected from
R5, R6 and R7are each independently selected from —H, methyl and Br;
or a pharmaceutically acceptable salt thereof.

### Claim 21

A compound of formula IC
wherein:
R1 is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, imidazopyridinyl, pyrazolopyridinyl or dihydropyrrolopyridinyl optionally substituted with oxo, wherein each heterocycle is optionally independently substituted with one to three groups selected from Ra, Rb and Rc;
R2 is C1-C6 alkyl or C3-6 cycloalkyl optionally substituted with C1-3 alkyl;
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9 or 5-6 membered heteroaryl ring which is optionally substituted with C1-3 alkyl;
R4, R6, and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6 cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6 cycloalkyl
(i) —S(O)nC1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2 heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a 5-6 membered heterocyclic ring;
R8 and R9 are each independently selected from —H, C1-6alkyl, and 5-6 membered heterocyclic ring;
Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, 13 S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with halogen and C1-6alkyl-aryl;
n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 21)

A compound of formula (IC) according to claim 21, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from:
R2 is methyl, ethyl, propyl, isopropyl, dimethylpropyl, butyl, t-butyl, isobutyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein the cycloalkyl group is optionally substituted with a C1-3 alkyl group;
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein the heteroaryl ring is optionally substituted with C1-3 alkyl;
R4, R6 and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6 cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6 cycloalkyl
(i) —S(O)nC1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
R8 and R9 are each independently selected from —H, C1-6alkyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
Ra is selected from H, —NH2, —NH(C1-6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, oxo and —CH2—OH;
Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
Rc is selected from —H, —CH3 and, —OH;
R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-fluoropyridine and C1-6alkyl-phenyl;
n is 0,1 or 2.

### Claim 23 (depends on 21)

A compound of formula (IC) as described in claim 21, wherein:
R1 is selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 21)

A compound of formula (IC) as described in claim 21, wherein:
R2 is methyl, ethyl, propyl, isopropyl, dimethylpropyl, butyl, t-butyl or isobutyl;
or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 21)

A compound of formula (IC) as described in claim 21, wherein:
R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein the heteroaryl ring is optionally substituted with C1-3 alkyl;
R4, R6 and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
(g) C3-6cycloalkyl
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6 cycloalkyl
(i) —S(O)2C1-6alkyl,
(j) —S(O)2aryl
(k) —S(O)2 heterocycle
(l) —CO2R8,
(m) —SCF3,
(n′) a pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
R8 and R9 are each independently selected from —H, C1-6alkyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl and tetrahydropyranyl;
or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 21)

A compound of formula (IC) as described in claim 21, wherein:
R1 is selected from:
R2 is t-butyl;
R3 is —H or halogen;
R4, R6and R7 are each independently selected from
(a) —H,
(b) —OH,
(c) halogen,
(d) —CN,
(e) —CF3,
(f) C1-6alkyl;
(g) C3-6 cycloalkyl,
(h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6 cycloalkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 26)

A compound of formula (IC) as described in claim 26, or a pharmaceutically acceptable salt thereof,
wherein R1 is

### Claim 28 (depends on 26)

A compound of formula (IC) as described in claim 26, wherein:
R2 is t-butyl;
or a pharmaceutically acceptable salt thereof.

### Claim 29 (depends on 26)

A compound of formula (IC) according to claim 26, wherein:
R1 is
R2 is t-butyl;
R3 is F;
R4, R6 and R7 are each independently selected from —H, Br and methoxy;
or a pharmaceutically acceptable salt thereof.

### Claim 30

A compound selected from a group consisting of:
or pharmaceutically acceptable salts thereof.

### Claim 31 (depends on 30)

A compound according to claim 30, selected from a group consisting of:
or pharmaceutically acceptable salts thereof.

### Claim 32 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient and/or carrier.

### Claim 33 (depends on 11)

A pharmaceutical composition comprising a compound according to claim 11, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient and/or carrier.

### Claim 34 (depends on 21)

A pharmaceutical composition comprising a compound according to claim 21, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient and/or carrier.